Elsevier

Sleep Medicine Clinics

Volume 4, Issue 2, June 2009, Pages 143-163
Sleep Medicine Clinics

Influence of the Circadian System on Disease Severity

https://doi.org/10.1016/j.jsmc.2009.02.005Get rights and content

The severity of many diseases varies by time of day. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night, and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, or endogenous circadian rhythms in physiology, or a combination of both. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease, and certain cancers in shift workers. This article describes the magnitude, relevance, and potential biologic basis of such daily changes in disease severity and of circadian/behavioral misalignment, and presents how these insights may help in the development of appropriate chronotherapy.

Section snippets

Day/night Rhythm in Adverse Cardiovascular Events, Arrhythmias, and Blood Pressure

Cardiovascular disease is the leading cause of death in the United States. Myocardial ischemia (insufficient supply of oxygenated blood relative to the demand of the cardiac muscle) can be caused by hypoxia, by coronary vasospasm, or by rupture of an atherosclerotic plaque and subsequent thrombosis affecting the coronary circulation. In extreme cases “sudden cardiac death” can result from an ischemic event in association with severe myocardial infarction or ventricular tachycardia/fibrillation.

Day/Night Rhythm in Asthma Severity

Bronchial asthma can be quite unstable especially when untreated. Asthmatic events occur most frequently during the night.74 More severe asthma is associated with more nocturnal symptoms.75 Patients with nocturnal asthma demonstrate increased morbidity and mortality relative to patients without noticeable worsening of asthma at night.76 Asthma has three defining components: chronic inflammation, airway hyperresponsiveness, and reversible airway obstruction.77 Each of these parameters exhibit

Cancer

Existing epidemiologic data indicate a link between various physiologic parameters having well-established day/night rhythms and carcinogenesis. For example, Rafnsson and colleagues117 found a higher rate of breast cancer in female flight attendants and female shift workers than in other women. Severely disrupted rest/activity cycles in patients with metastatic colorectal cancer is accompanied by decreased survival compared with patients with a well-preserved rest/activity pattern.118 A number

Epilepsy

Epilepsy is another disorder that often exhibits a day/night variation in clinical presentation. Pavlova and colleagues134 found that temporal lobe epileptic seizures occur more frequently between 3 and 7 pm, whereas the peak incidence for extra–temporal lobe epileptic seizures occurs between 7 and 11 pm. Among those seizures that occurred during sleep, the majority originated in the temporal lobe.134 Similarly, analysis of 131 adults with localized epilepsy revealed that the day/night

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease that occurs during wakefulness is usually postprandial and rapidly cleared. Nocturnal gastroesophageal reflux events occur less frequently than those occurring during the daytime but are associated with longer acid-clearance time139 due to sleep or circadian-related decreases in swallowing,140 saliva production (saliva contains mucous and bicarbonates that neutralize acid from the stomach),141 peristalis142 and reduced symptoms of heartburn such that protective

Alzheimer's Disease

Alzheimer's disease affects about 15 million people worldwide and is most commonly seen after the age of 50, with progressive cognitive decline, and circadian rhythm and sleep disturbances, including insomnia. It is tragic for the patient, causes major physical and emotional burden for primary caregivers, and represents a large economic burden for society. The most common reason for institutionalizing patients with Alzheimer's disease is need for care during the night, stemming from altered

Effect of circadian misalignment on health

About 10% of the United States labor force works rotating, irregular, or permanent night shifts. Shift work is generally associated with chronic misalignment between the endogenous circadian timing system and the behavioral cycles, including sleep/wake and fasting/feeding cycles. Thus, such people may be attempting to sleep during the daytime at a circadian phase better for activity and, conversely, attempting to remain awake during the night at a circadian phase better for sleep and fasting.

Summary and Future Directions

We have reviewed (1) how interactions between the circadian and behavioral systems affect disease severity, notably the day/night pattern of adverse cardiovascular events, seizures, and asthma exacerbations; (2) how a disease can affect circadian rhythmicity, notably the circadian disruption of Alzheimer's disease; and (3) the adverse health consequences of circadian misalignment, typical of chronic shift work. In each case, chronotherapeutic considerations are presented. With a few notable

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    This work was supported by grant K24 HL76446 from the National Institutes of Health to SA Shea, by grant R21 AT002713 from the National Institutes of Health to FAJL Scheer, and by grant 43-PA-08 from the American Sleep Medicine Foundation (a foundation of the American Academy of Sleep Medicine) to M Litinski.

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